1. Field of the Invention
The present invention relates to nebulizers, for example, for atomizing a drug for inhalation by patient, whereby the atomized drug is administered to a patient through deposition in his lungs, and to methods of loading nebulizers. The subject and may be a powder, a liquid, or a particulate suspension, but is not limited only to these three forms of substance. In this specification, references to the drug being in a particular form, such as “liquid” or “droplet” is to be understood to also include the other forms, unless specified otherwise.
2. Brief Description of Art
Several different types of nebulizer are known, the most common being pneumatically operated nebulizers which are operated from a compressed air source connected to the nebulizer. Other types of nebulizer include ultrasonic type nebulizers which use a piezo electric crystal to atomize the substance, mesh-type nebulizers which force the substance in liquid form through a fine mesh in order to create droplets, electrohydrodynamic (EHD) nebulizers and capillary microjet nebulizers.
For medical use where a drug is delivered to the lungs of a patient, the optimum diameter of the medication particles or droplets is about 1-5 microns. If the particles or droplets are bigger than this, they tend to impact the patient's airways before they reach the lungs, but if they are smaller than this range, they enter the lung during inhalation, and tend to be carried out of the lungs again on exhalation without sedimenting in the lungs. For the best result, as greater proportion of the drug must reach and sediment as deep inside the lung as possible.
Each of the types of nebulizer has its own advantages and disadvantages. For example, common pneumatic type nebulizers are typically only 50% efficient at releasing the nebulized drug in suitable sized droplets from the reservoir, and require baffles to collect oversized droplets which coalesce and run back into the reservoir for recirculation. By contrast, mesh-type nebulizers will often have an efficiency of around 90%. Other types of nebulizer also have a high efficiency, where a very high proportion of the nebulizer drug is in the correct droplet size range, such as electrohydynamic nebulizers and capillary microjet nebulizers. None of these nebulizers needs to re-circulate the drug, and so they might be described as single pass nebulizers.
However, pneumatic nebulizers can be developed to have an output rate which does not vary significantly throughout the life of the apparatus, which means that the amount of drug delivered to a patient during a treatment can be measured accurately so that when the prescribed amount of drug has been delivered to the patient's lungs, nebulization can automatically stop. One such measurement arrangement is known as Adaptive Aerosol Delivery™, and is present in a nebulizer sold by Medic-Aid Limited under the name Halolite, and is the subject of European Patent Application No. 97927296 and European Patent Application No. 99950992, the contents of both of which we incorporate herein by reference in their entireties.
However, the output rate of a mesh-type nebulizer will often deteriorate over the life of the nebulizer since the mesh holes may become blocked, which affects the rate of delivery. Therefore, a pre-calibrated rate of nebulizer output as used in the Adaptive Aerosol Delivery™ system described briefly above is not always appropriate. Instead, it is appropriate to fill a reservoir with a pre-set dose for delivery to the patient. Once all of the dose has been delivered, the treatment is complete. The same issue applies to EHD nebulizers and capillary microjet nebulizers in terms of the number of sites of aerosol generation varying over the lifetime of the product. In the EHD system, any disruption n the electrostatic field generated can cause the production of fewer cones which form the nebulization sites, and this will change the output rate. In the case of capillary microjet nebulizers, a large number of microjets are required, usually several hundred, to produce an aerosol with sufficient mass output. Blockage of individual microjets will affect the rate of output of the produce.
Since pneumatic nebulizers are much more popular than mesh-type nebulizers, many existing drug preparations have been developed for pneumatic nebulizers, but the volume of drug in these preparations is far too great for use with mesh-type nebulizers. Clearly, it is important for safe use of these devices that a simple and reliable method of metering the drug is used.
WO 99/63946 discloses a mesh-type nebulizer, the operation of which is bet seen in FIG. 3 of that application. A mesh is mounted across an aperture, and the nebulizer is arranged such that piezo electric element is used to vibrate the mesh. When a droplet of liquid is placed on the rear surface of the mesh, the vibrations from the piezo electric element causes the liquid to pass through the holes in the mesh forming droplets which are released from the front surface of the mesh.
EP 1142600 A1 discloses a spray forming device in which a liquid is fed through a pipe into a narrow space between a mesh and a piezo electric element. The mesh includes holes through which the liquid passes when the piezo electric element vibrates.
Examples of EHD and capillary microjet nebulizers can be found in WO 00/38770 and U.S. Pat. No. 6,119,953 respectively, which are incorporated herein by reference in their entireties.
A pneumatic nebulizer is shown in EP 0627266 A2 in which air from a pressurized air source issues from an air outlet hole around which are disposed holes through which the liquid to be atomized is drawn out from a main reservoir. Each of those holes is within a groove forming a secondary reservoir around the air outlet hole. A deflector bar is located across and in the path of the air issuing from the air outlet so that as it issues from the air outlet, it is immediately deflected across the top of the liquid outlet holes, thereby creating low pressure regions, thereby drawing the liquid up from the main reservoir beneath, and atomizing that liquid as it is drawn from the holes. The droplets generated in this way are carried to a patient fro inhalation. Atomization can be switched on and off by switching on and off the pressurized air supply to the nebulizer.